The landscape of genomic alterations across childhood cancers
The landscape of genomic alterations across childhood cancers
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DOI：
10.1038/nature25480
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发表时间：
2018-03-15
期刊：
影响因子：
64.8
通讯作者：
Pfister, Stefan M.
中科院分区：
文献类型：
--
作者：
Groebner, Susanne N.;Worst, Barbara C.;Pfister, Stefan M.
泛癌症分析检查各种癌症类型之间的共性和差异，已成为获得癌症生物学新见解的有力途径。在这里，我们提出了一个泛癌症队列的遗传变异的综合分析，包括961个来自儿童，青少年和年轻人的肿瘤，包括24种不同的分子类型的癌症。使用标准化的工作流程，我们确定了与先前分析的成人癌症相比在突变频率和显著突变基因方面的显著差异。149个推定的癌症驱动基因的遗传改变将肿瘤分为两类：小突变和结构/拷贝数变异（与种系变异相关）。结构变体、超二倍体和染色体断裂与TP 53突变状态和突变特征相关。我们的数据表明，该队列中7-8%的儿童携带明确的易感生殖系变异，近50%的儿科肿瘤具有潜在的药物事件，这与未来临床试验的设计高度相关。
Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.